GLUTAMATE-STIMULATED ROS PRODUCTION IN NEURONAL CULTURES - INTERACTIONS WITH LEAD AND THE CHOLINERGIC SYSTEM

Oxidative stress may be an important factor in several pathological br ain conditions. A contributing factor in many such conditions is exces sive glutamate release, and subsequent glutamatergic neuronal stimulat ion, that causes increased production of reactive oxygen species (ROS) , oxidative stress, excitotoxicity and neuronal damage. Glutamate rele ase is also associated with illnesses such as Alzheimer's disease, str oke, and brain injury. Glutamate may interact with an environmental to xin, lead, and this interaction may result in neuronal damage. Glutama te-induced ROS production is greatly amplified by lead in cultured neu ronal cells. Alterations in protein kinase C (PKC) activity seem to be important both for glutamate-induced ROS production, and for the ampl ification of glutamate-induced ROS production by lead. It is possible that the neurotoxic effects of lead are amplified through glutamate-in duced neuronal excitation. Cholinergic stimulation can also trigger RO S production in neuronal cells. PKC seems to play a key-role also in c holinergic-induced ROS production superoxide anion being the primary r eactive oxygen species. There seems to be a close relationship between the responses of cholinergic muscarinic and glutamatergic receptors b ecause glutamate receptor antagonists inhibit cholinergic-induced acti vation of human neuroblastoma cells. Glutamatergic neuronal stimulatio n may be a common final pathway in several brain conditions in which o xidative stress and ensuing excitotoxicity plays a role. (C) 1998 Inte r Press, Inc.